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Research in the treatment and causes of schizophrenia

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Vishwajit L Nimgaonkar, MD, PhD …

Vishwajit L Nimgaonkar, MD, PhD
Professor of Psychiatry and Human Genetics, University of Pittsburgh

Medicine, Culture, and Spirituality Conference
September 9, 2011

Published in: Health & Medicine

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  • 1. Research in the treatment and causes of schizophrenia Vishwajit L Nimgaonkar, MD, PhD Professor of Psychiatry and Human Genetics, University of Pittsburgh [email_address]
  • 2. Disclosure statement
    • Vishwajit L. Nimgaonkar
    • has no conflict of interest in this presentation
  • 3. Outline (vignettes)
    • Diagnosis
    • Treatment
    • Causation
    • Research at Pittsburgh
    • Request for your help
  • 4. Outline
    • Diagnosis
    • Treatment
    • Causation
    • Research at Pittsburgh
    • Request for your help
  • 5. Empirical Diagnosis (DSM IV)
    • Two or more psychotic features: > 1 month
    • Impaired social / occupational function
    • Duration (6 months)
    • Exclude:
      • Mood disorder, possible causative medical condition, substance abuse.
  • 6. Coming soon …
    • DSM V criteria (due 2012)
      • Lifespan diagnostic approach.
      • Emphasis on dimensional concepts.
      • Diagnostic specificity.
      • Interface between psychiatric and general medicine.
      • Gender and cross-cultural issues.
      • Remove schizoaffective disorder?
  • 7. Outline:
    • Diagnosis
    • Treatment
    • Causation
    • Research at Pittsburgh
    • Request for your help
  • 8. Patient Outcomes Research Team (PORT, Lehman et al, 1995 ….)
    • Medications: Buchanan et al, 2010.
      • http://www.ncbi.nlm.nih.gov/pubmed/19955390?dopt=Citation
    • Psychosocial Rx: Dixon et al, 2010.
      • http://schizophreniabulletin.oxfordjournals.org/content/36/1/48.full.pdf+html
    • Levels of adherence?
  • 9. Antipsychotic drugs
    • Most significant benefit:
      • PREVENTION OF RELAPSE
    • Symptomatic improvement
    • Modest improvement:
      • ‘ negative’ symptoms
      • cognitive features
      • social function
    • Efficacy / side effect profiles vary between patients.
  • 10. Classical: first generation antipsychotic drugs
    • Chlorpromazine (Largactil)
    • Haloperidol (Haldol)
    • Fluphenazine (Prolixin)
    • Ziprasidone (Geodon)
    • Clozapine (Clozaril): treatment resistant schizophrenia
  • 11. Second generation antipsychotic drugs
    • Risperidone (Risperdal)
    • Olanzapine (Zyprexa)
    • Quetiapine (Seroquel)
  • 12. Most recent antipsychotic drugs
    • Aripiprazole (Abilify)
    • Paliperidone (Invega)*
    • Asenapine (Saphris)
    • Iloperidone (Fanapt)
    • Lurasidone (Latuda)
    • * Risperidone metabolite
  • 13. ‘ Newest’ antipsychotic drugs* * Cindy Holway, PharmD, MBA Drug Advantages Side effects/concerns Asenapine (Saphris) Sublingual, rapid absorption. Akathisia, oral hypoesthesia, somnolence. ? Hemodynamics. Iloperidone (Fanapt) Low EPS, low akathisia, little weight gain. Dizziness, orthostasis. ? QT prolongation. Lurasidone (Latuda) Pregnancy category B, low weight gain, low extra pyramidal symptoms. Akathisia, nausea. ? Use in moderate / severe renal impairment.
  • 14. Adjunctive treatments (PORT, Dixon et al, 2010)
    • Assertive Community Treatment
    • Supported Employment
    • Skills training
    • Cognitive Behavioral Therapy (+/-)
    • Token Economy Interventions (old data)
    • Family-Based Services
    • Alcohol and Substance Use Disorders
    • Weight Management
  • 15. More evidence needed (PORT, Dixon et al, 2010)
    • Cognitive remediation
    • Peer Support and Peer-Delivered Services
    • Interventions to Increase Adherence to Antipsychotic Medication
    • Psychosocial Treatments for Recent Onset Schizophrenia
  • 16. Outline
    • Diagnosis
    • Treatment
    • Causation
    • Research at Pittsburgh
    • Request for your help
  • 17. Genetics: ‘tsunami’
    • Increased number of polymorphisms:
      • genome-wide association studies (GWAS) ~1 million SNPs / person
    • Coming soon: Whole genome sequencing.
  • 18. GWAS: HLA variants and schizophrenia
  • 19. HLA variants in schizophrenia: Pittsburgh studies
  • 20. Copy number variations in schizophrenia
      • Odds ratios ~ 7 – 13
      • Chromosome 22q11.2
      • Chr. 1q21.1
      • Chr.15q11.2
      • Chr. 15q13.3 (autism / Angelman-Prader Willi S)
  • 21. Antibodies to Toxoplasma gondii in Patients with Schizophrenia: Meta-Analysis
    • Torrey et al., Schizophr Bulletin (2007), 33 (3): 729-736.
    • Forty-two studies: 17 countries over 5 decades; 23 met selection criteria.
    • Combined odds ratio (OR): 2.73
    • (95% C.I., 2.10 to 3.60; p < .000001).
  • 22. Outline
    • Diagnosis
    • Treatment
    • Causation
    • Research at Pittsburgh
    • Request for your help
  • 23. Abnormalities in the auditory cortex
    • Robert A. Sweet, M.D.
    • (Professor of Psychiatry and Neurology, Co-Associate Director for Research, MIRECC, VA Pittsburgh Healthcare System)
  • 24. Small molecule modulation of dendritic spine structural plasticity to enhance persistence and prevent loss Prevention Auditory Cortex Clinical Feature Pathophysiology Pathology Vocal Emotion Discrimination Pitch Discrimination Pathogenesis Affective Impairment
  • 25.
    • K.N. Roy Chengappa, MD.
    • (Professor of Psychiatry, University of Pittsburgh)
    • L-Carnosine – A potent antioxidant has shown benefits for improving cognitive set-shifting and decreasing perseverative errors in a subgroup of people with schizophrenia.
      • Unpublished.
    Cognitive remediation: medications
  • 26. Anti-herpes virus specific treatment and cognition in schizophrenia: a test-of-concept randomized double blind placebo controlled trial K M Prasad MD Assistant Professor of Psychiatry University of Pittsburgh ( unpublished)
  • 27. Changes in neuropsychological scores with Valacyclovir ‘add on’
  • 28. Yoga for cognitive remediation
    • Bhatia et al, in press, Acta Psychiatrica Scandinavica
    • Federally funded trial in India
      • conventional exercise as comparison
      • random allocation to treatment cells
      • ‘ blind’ evaluation
    • Pilot studies in the USA?
  • 29. Outline
    • Diagnosis
    • Treatment
    • Causation
    • Research at Pittsburgh
    • Request for your help
  • 30.
    • Comprehensive study of causation and pathogenesis
      • Includes patients, relatives, controls
      • Diagnostic studies
      • Computerized cognitive evaluation
      • MRI studies
      • Genetic and environmental studies
      • Federally funded (NIMH)
    A Family Study of Schizophrenia and Related Conditions
  • 31. Participation details
        • Families with > 2 closely related members with schizophrenia / schizoaffective disorder
          • Parent / child; siblings
          • All relatives eligible
        • Caucasian ethnicity
        • Voluntary and confidential .
        • No change in treatment.
        • One time.
        • Participant receive $ 175 + travel costs.
  • 32. A Family Study of Schizophrenia and Related Conditions Please visit our table at the conference TOLL FREE: 1-877-363-5895 Fax: (412) 246 6350 WEB SITE: www.pitt.edu/~nimga